DESCRIPTION (APPLICANT'S ABSTRACT): Complementary and alternative medicine (CAM) has recently gained popularity with the American public. Research validating CAM has focused mainly on the treatment and prevention of systemic medical diseases while less attention has been paid to oral diseases. Oral diseases including dental caries and periodontal disease, are a major cause of loss of work and school days. Chemical and mechanical means have been used to control dental plaque bacteria, the etiologic agent of caries and periodontal disease. However, none of the available agents is ideal and frequently cause adverse effects. This justifies further search and development of alternative agents from natural sources that are safe and effective. The North American plant, Hydrastis canadensis L. (Ranunculaceae), known commercially as "Goldenseal," has been used for centuries as an antiseptic to treat skin disorders and as an antidiarrheal, antiseptic, astringent, hemostatic, and vasoconstrictor agent. Goldenseal is one of the major phytomedicines ("herbal remedies") sold in health food stores and pharmacies in the U.S. Several mouthrinses and toothpastes containing Goldenseal are available on the market. Although claims have been made by the manufactures regarding its ability to fight gum diseases and prevent caries, no scientific data is available to substantiate these claims. The goal of the proposed research is to evaluate the potential of Goldenseal as a remedy in prevention and treatment of oral diseases and to maintain oral health. It is hypothesized that antimicrobial compounds that are safe for humans can be identified from H. canadensis. These compounds may have potential as dental prophylactic/therapeutic agents and may also serve as lead compounds for the subsequent design and synthesis of new agents that are even more effective than the existing ones. The Specific Aims of this study are: SA1: To isolate and identify active antimicrobial compounds from H. canadensis by activity-guided fractionation and characterization; SA2: To determine antimicrobial activity of the purified compounds against cariogenic and periodontal pathogens; SA3: To investigate mixtures of purified antimicrobial compounds from H. canadensis for synergistic antimicrobial activities; SA4: To correlate bioactivity of various commercially available Goldenseal-containing oral hygiene products with levels of active alkaloids identified in SA2. The proposed research is innovative in that it represents collaboration between an oral microbiologist and a natural product chemist that will assure the speedy discovery of novel or known active compounds from Goldenseal and will provide scientific explanation as to the remedy's efficacy. It will also serve as a model system for the evaluation of existing herbal remedies for their oral health related claims. This application of CAM research will help to achieve better oral health and oral disease prevention, one of the to priority areas of focus specified b the U.S. Public Health Service in "Health People 2000."